The instant invention relates to diagnostic agents which are highly useful and highly sensitive for the clinical diagnosis of primary hepatoma as distinguished from metastatic and other liver disease. More particularly, the invention relates to new serological diagnostic agents for the determination of primary hepatoma, which are based on anti-.alpha.1-fetoglobulin. This invention also relates to methods for the preparation of said serological diagnostic agents. Furthermore, this invention relates to diagnostic methods which depend upon the use of said diagnostic agent.
Originally, it was found that the serum of the cattle fetus contained a type of .alpha.1-globulin which was designated .alpha.1-fetoglobulin (Fetuin) [K. O. Pedersen, Nature 154, 575 (1944)]. It was then discovered that this particular substance also occurred in the sera of fetuses of different animal species and was specific to various species. Those findings were followed by the discovery that the same substance also occurred in the serum of the human fetus, C. G. Bergstrand, et al., J. Clin. & Lab. Invest. 8 174 (1956). Recently, it was further demonstrated by immunological precipitin reactions, that .alpha.1-fetoglobulin occurs in the sera of patients having primary hepatoma [Yu. S. Tatarinov, Vop. Med. Khim. 11 (2) 20 (1965) and others ]. It has thus been suggested that the presence or absence of .alpha.1-fetoglobulin may provide a test for primary hepatoma. Over the succeeding years, we conducted extensive research into the basic mechanism of these cancers on the strength of the finding that metabolism of the human being afflicted with the cancerous diseases are analogous to that of the fetus, and that .alpha.1-fetoglobulin is closely related to primary hepatoma. Our effort has been largely concentrated on the development of improved diagnostic agents for clinical use.